The American Cancer Society (ACS) estimates that in 2020, 276,480 women will be diagnosed with breast cancer in the U.S. Every two minutes an American woman is diagnosed with breast cancer and 42,170 dies each year. Although about 100 times less common than in women, breast cancer also affects men. The ACS estimates that the lifetime risk of men getting breast cancer is about 1 in 1,000; 2,620 new cases of invasive breast cancer will be diagnosed in 2020, and 520 men will die from breast cancer in 2020.

Seattle-based Atossa Therapeutics, Inc. (ATOS), a clinical-stage biopharmaceutical company developing novel therapeutics and delivery methods to treat breast cancer and other breast conditions, today announced its recent progress with its Phase 2 study administering oral Endoxifen in the “window of opportunity” between diagnosis of breast cancer and surgery, as well as the company’s proposed Phase 2 clinical trial to reduce mammographic breast density (MBD).

Atossa’s Phase 2 study of its oral Endoxifen in the window of opportunity between diagnosis of breast cancer and surgery is currently being conducted in Australia. The study will enroll up to 25 newly-diagnosed patients with ER+ and human epidermal growth factor receptor 2 negative (HER2-) stage 1 or 2 invasive breast cancer, requiring mastectomy or lumpectomy. Patients will receive Atossa’s proprietary oral Endoxifen for at least 14 days from the time of diagnosis up to the day of surgery. The primary endpoint is to determine if the administration of oral Endoxifen reduces the tumor activity as measured by Ki-67 (a measure of cellular proliferation that correlates with tumor growth). A small study showed that a reduction of Ki-67 during the window of opportunity suggests a better outcome in these patients (Fasching et al. BMC Cancer 2011, 11:486). The secondary endpoints are safety and tolerability and assessment of the study drug on expression levels of both estrogen and progesterone receptors. The impact on additional markers of cellular activity will also be explored. The Phase 2 study is being conducted on behalf of Atossa by Avance Clinical, which successfully completed four Phase 1 studies of Atossa’s Endoxifen.

Completed treating a sufficient number of patients to permit an initial report of study results from the pilot portion of the study.

Contracted with Avance Clinical to open a second site for the study in Geelong, Victoria, Australia, with the goal of increasing the rate of enrollment.

Applied to the Institutional Review Board for approval to open the second site in Geelong, Australia.

Manufactured sufficient Endoxifen necessary for all patients expected to enroll in this study.

The primary objective of the company’s MBD study is to determine if breast density changes compared to placebo and among different doses, with secondary endpoints to assess and characterize safety and tolerability. South General Hospital in Stockholm, Sweden will be conducting this study at multiple sites, after having recently completed the company’s Phase 2 study of its topical form of Endoxifen. The study is being led by principal investigator Per Hall, M.D., Ph.D., Head of the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.

Legislation that has been recently enacted in over 40 states requiring that women be notified if they have MBD. These notifications typically state that women with MBD have a higher risk of developing breast cancer, and that mammography may not be as effective in detecting breast cancer because the MBD can “mask” the detection of cancers. In February 2019, Federal legislation was enacted that requires that the FDA adopt rules requiring that mammography reports include information about breast density and inform women about their breast density.

Updates on Atossa’s planned Phase 2 trial to reduce MBD include:

In February 2020, they applied with the Swedish regulatory authorities (the MPA and IRB) for approval to begin our Phase 2 clinical study of their oral Endoxifen to reduce MBD.

The MPA provided questions about their application, as is typical, and they will be addressing those questions over the coming weeks. Because of the outbreak of COVID-19, health facilities in Sweden are not currently providing screening mammograms.

As a practical matter, they cannot begin enrolling patients until screening mammograms recommence in Stockholm. They plan to begin this study as soon as they receive approval from the Swedish regulatory authorities and screening mammograms recommence.

Atossa has manufactured all of the drug necessary for three months of dosing for the first 90 patients to be enrolled in the planned Phase 2 study.

Additionally, Atossa submitted materials to the FDA in advance of its scheduled April 30 meeting and has confirmed at least three years of stability data on its proprietary Endoxifen.

“We are very pleased with the recent progress, Once a patient is diagnosed with early-stage breast cancer, it typically takes two to three weeks for surgery. During that time, the tumor continues to grow and we believe there is a compelling opportunity to treat these women during this ‘window of opportunity’ to reduce the tumor growth activity. Now that we have completed the treatment on a sufficient number of patients in the WOO study, we look forward to reporting initial study results. Last year, we provided oral Endoxifen on a ‘compassionate use’ basis to a pre-menopausal woman in the United States during this window of opportunity and saw a 50% reduction in tumor cell activity, as measured by Ki-67.” Dr. Steven Quay, Atossa’s President, and Chief Executive Officer.

It has been estimated that approximately ten million women in the United States have MBD, for which there is no FDA-approved treatment. Although oral tamoxifen is approved to prevent breast cancer in “high-risk” women (typically based on responses to a questionnaire), it is used by less than 5% of women with an increased risk of developing breast cancer because of the actual or perceived side effects and risks of tamoxifen. We believe our Endoxifen may provide an option for women to proactively reduce the density of their breasts. Moreover, our Endoxifen may improve mammography accuracy and patient care by unmasking cancerous tumors that are otherwise hidden by breast density.